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1.
Int J Mol Sci ; 22(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671651

RESUMO

By dint of the aging population and further deepened with the Covid-19 pandemic, lung disease has turned out to be a major cause of worldwide morbidity and mortality. The condition is exacerbated when the immune system further attacks the healthy, rather than the diseased, tissue within the lung. Governed by unremittingly proliferating mesenchymal cells and increased collagen deposition, if inflammation persists, as frequently occurs in aging lungs, the tissue develops tumors and/or turns into scars (fibrosis), with limited regenerative capacity and organ failure. Fas ligand (FasL, a ligand of the Fas cell death receptor) is a key factor in the regulation of these processes. FasL is primarily found in two forms: full length (membrane, or mFasL) and cleaved (soluble, or sFasL). We and others found that T-cells expressing the mFasL retain autoimmune surveillance that controls mesenchymal, as well as tumor cell accumulation following an inflammatory response. However, mesenchymal cells from fibrotic lungs, tumor cells, or cells from immune-privileged sites, resist FasL+ T-cell-induced cell death. The mechanisms involved are a counterattack of immune cells by FasL, by releasing a soluble form of FasL that competes with the membrane version, and inhibits their cell death, promoting cell survival. This review focuses on understanding the previously unrecognized role of FasL, and in particular its soluble form, sFasL, in the serum of aged subjects, and its association with the evolution of lung disease, paving the way to new methods of diagnosis and treatment.


Assuntos
/imunologia , Proteína Ligante Fas/imunologia , Pneumopatias/imunologia , Pulmão/imunologia , Fatores Etários , Idoso , Morte Celular/imunologia , Proteína Ligante Fas/sangue , Humanos , Imunidade , Pneumopatias/sangue , /isolamento & purificação , Linfócitos T/imunologia
2.
Crit Care ; 25(1): 53, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33557908

RESUMO

The current pandemic of COVID-19 caused thousands of deaths and healthcare professionals struggle to properly manage infected patients. This review summarizes information about SARS-CoV-2 receptor binding dynamics and intricacies, lung autopsy findings, immune response patterns, evidence-based explanations for the immune response, and COVID-19-associated hypercoagulability.


Assuntos
/fisiopatologia , Proteínas de Transporte/fisiologia , Pneumopatias/fisiopatologia , Pneumonia Viral/fisiopatologia , /patogenicidade , /imunologia , Proteínas de Transporte/imunologia , Humanos , Pneumopatias/imunologia , Pandemias , Pneumonia Viral/imunologia , /imunologia
3.
Oxid Med Cell Longev ; 2021: 6646923, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628371

RESUMO

Inflammatory lung disease results in a high global burden of death and disability. There are no effective treatments for the most severe forms of many inflammatory lung diseases, such as chronic obstructive pulmonary disease, emphysema, corticosteroid-resistant asthma, and coronavirus disease 2019; hence, new treatment options are required. Here, we review the role of oxidative imbalance in the development of difficult-to-treat inflammatory lung diseases. The inflammation-induced overproduction of reactive oxygen species (ROS) means that endogenous antioxidants may not be sufficient to prevent oxidative damage, resulting in an oxidative imbalance in the lung. In turn, intracellular signaling events trigger the production of proinflammatory mediators that perpetuate and aggravate the inflammatory response and may lead to tissue damage. The production of high levels of ROS in inflammatory lung diseases can induce the phosphorylation of mitogen-activated protein kinases, the inactivation of phosphoinositide 3-kinase (PI3K) signaling and histone deacetylase 2, a decrease in glucocorticoid binding to its receptor, and thus resistance to glucocorticoid treatment. Hence, antioxidant treatment might be a therapeutic option for inflammatory lung diseases. Preclinical studies have shown that antioxidants (alone or combined with anti-inflammatory drugs) are effective in the treatment of inflammatory lung diseases, although the clinical evidence of efficacy is weaker. Despite the high level of evidence for the efficacy of antioxidants in the treatment of inflammatory lung diseases, the discovery and clinical investigation of safer, more efficacious compounds are now a priority.


Assuntos
Antioxidantes/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Pneumopatias/tratamento farmacológico , Pneumopatias/metabolismo , Animais , Humanos , Inflamação/imunologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pneumopatias/imunologia , Oxirredução/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Espécies Reativas de Oxigênio/metabolismo
6.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370993

RESUMO

We report a novel case of a patient who presented with new diagnoses of both cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) positive vasculitis and chronic lymphocytic leukaemia (CLL). The patient was a 79-year-old man who presented with melena, haemoptysis, acute hypoxia and acute kidney injury. In the current literature, there are rare associations of c-ANCA vasculitis and malignancy, but very few, if any, relating c-ANCA vasculitis and CLL. This case is unique due to the presence of both pathologies and an uncommon presentation of the vasculitis. He presented with renal and pulmonary findings, unlike the dermal manifestations commonly seen with vasculitis. We think that this could be an easily overlooked combination of diseases and, therefore, the purpose of this case is to prevent delays in care that could affect patient outcomes and also to encourage further research into the relationship between these diseases.


Assuntos
Lesão Renal Aguda/diagnóstico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos/sangue , Leucemia Linfocítica Crônica de Células B/diagnóstico , Pneumopatias/diagnóstico , Melena/imunologia , Lesão Renal Aguda/imunologia , Lesão Renal Aguda/patologia , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Biópsia , Medula Óssea/patologia , Quimioterapia Combinada/métodos , Humanos , Rim/patologia , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/imunologia , Pulmão/diagnóstico por imagem , Pneumopatias/imunologia , Masculino , Melena/diagnóstico , Prednisona/uso terapêutico , Rituximab/uso terapêutico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
7.
J Transl Med ; 18(1): 297, 2020 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-32746922

RESUMO

BACKGROUND: The severe acute respiratory syndrome virus SARS-CoV-2, a close relative of the SARS-CoV virus, is the cause of the recent COVID-19 pandemic affecting, to date, over 14 million individuals across the globe and demonstrating relatively high rates of infection and mortality. A third virus, the H5N1, responsible for avian influenza, has caused infection with some clinical similarities to those in COVID-19 infections. Cytokines, small proteins that modulate immune responses, have been directly implicated in some of the severe responses seen in COVID-19 patients, e.g. cytokine storms. Understanding the immune processes related to COVID-19, and other similar infections, could help identify diagnostic markers and therapeutic targets. METHODS: Here we examine data of cytokine, immune cell types, and disease associations captured from biomedical literature associated with COVID-19, Coronavirus in general, SARS, and H5N1 influenza, with the objective of identifying potentially useful relationships and areas for future research. RESULTS: Cytokine and cell-type associations captured from Medical Subject Heading (MeSH) terms linked to thousands of PubMed records, has identified differing patterns of associations between the four corpuses of publications (COVID-19, Coronavirus, SARS, or H5N1 influenza). Clustering of cytokine-disease co-occurrences in the context of Coronavirus has identified compelling clusters of co-morbidities and symptoms, some of which already known to be linked to COVID-19. Finally, network analysis identified sub-networks of cytokines and immune cell types associated with different manifestations, co-morbidities and symptoms of Coronavirus, SARS, and H5N1. CONCLUSION: Systematic review of research in medicine is essential to facilitate evidence-based choices about health interventions. In a fast moving pandemic the approach taken here will identify trends and enable rapid comparison to the literature of related diseases.


Assuntos
Betacoronavirus , Infecções por Coronavirus/imunologia , Pneumopatias/imunologia , Pneumonia Viral/imunologia , Publicações , Análise por Conglomerados , Comorbidade , Síndrome da Liberação de Citocina/virologia , Citocinas/imunologia , Células-Tronco Hematopoéticas/citologia , Humanos , Sistema Imunitário , Virus da Influenza A Subtipo H5N1 , Influenza Humana/imunologia , Pandemias , PubMed , Síndrome Respiratória Aguda Grave/imunologia
9.
Clin Immunol ; 218: 108524, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32659373

RESUMO

The outbreak of SARS-CoV-2-associated pneumonia, a disease called COVID-19, has caused a pandemic worldwide. To investigate the immune responses after infection of SARS-CoV-2 in non-critical patients may help to better understand the disease progression. We collected 334 confirmed COVID-19 cases including 212 still in hospital with nucleic acid test positive on halfway for SARS-CoV-2 and 122 discharged from hospital, compared specific antibodies, immune cells, and cytokine changes between the hospitalized and discharged patients. The hospitalized patients had a longer illness time compared with discharged patients. Analysis of viral loads explained long-term or persistent infection of SARS-CoV-2, which existed with the median time of 18.5 days of the positive nucleic acid test. Serum analysis showed that the specific anti-N IgG antibody was positive in all detected patients after infection of two weeks. Neutrophils, Monocytes, NK cells, and CD4+ T cells significantly increased, while total lymphocytes and CD8+ T cells decreased from non-critical hospitalized patients after longer-term infection. Further analysis of the cytokines showed that IL-6, TNF-α, IFN-γ, IL-2, IL-4, and IL-10 from the hospitalized patients were significantly higher, indicating a potential of the increased CD4+ T cell differentiation.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/imunologia , Infecções por Coronavirus/imunologia , Diabetes Mellitus/imunologia , Imunidade Inata , Pneumopatias/imunologia , Neoplasias/imunologia , Pneumonia Viral/imunologia , Idoso , Anticorpos Antivirais/sangue , Betacoronavirus/imunologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/patologia , Doenças Cardiovasculares/virologia , China/epidemiologia , Comorbidade , Convalescença , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Citocinas/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Feminino , Hospitalização , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Pneumopatias/epidemiologia , Pneumopatias/patologia , Pneumopatias/virologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/patologia , Subpopulações de Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Monócitos/virologia , Neoplasias/epidemiologia , Neoplasias/patologia , Neoplasias/virologia , Neutrófilos/imunologia , Neutrófilos/patologia , Neutrófilos/virologia , Pandemias , Alta do Paciente , Pneumonia Viral/epidemiologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fatores de Tempo , Carga Viral/imunologia
10.
mSphere ; 5(3)2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32581077

RESUMO

COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.


Assuntos
Betacoronavirus/imunologia , Quimiocinas/imunologia , Infecções por Coronavirus/imunologia , Inflamação/patologia , Neutrófilos/imunologia , Pneumonia Viral/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Quimiocinas/genética , Infecções por Coronavirus/patologia , Humanos , Inflamação/imunologia , Pneumopatias/imunologia , Pneumopatias/patologia , Infiltração de Neutrófilos/imunologia , Pandemias , Pneumonia Viral/patologia , Receptores Virais/genética
11.
BMC Infect Dis ; 20(1): 431, 2020 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-32563248

RESUMO

BACKGROUND: Good's syndrome (GS) is characterized by immunodeficiency, and can lead to severe infection, which is the most significant complication. Although Mycobacterium rarely causes infection in patients with GS, disseminated nontuberculous mycobacterial (NTM) infection frequently occurs in GS patients that are also positive for the human immunodeficiency virus (HIV) or anti-interferon (IFN)-γ autoantibodies. Here, we report a rare case of GS with NTM without HIV or IFN-γ autoantibodies. CASE PRESENTATION: A 57-year-old Japanese male with GS and myasthenia gravis (treated with prednisolone and tacrolimus) was diagnosed with disseminated NTM infection caused by Mycobacterium abscessus subsp. massiliense. He presented with fever and back pain. Blood, lumbar tissue, urine, stool, and sputum cultures tested positive for M. abscessus. Bacteremia, spondylitis, intestinal lumber abscess, and lung infection were confirmed by bacteriological examination and diagnostic imaging; urinary and intestinal tract infections were suspected by bacteriological examination but not confirmed by imaging. Despite multidrug combination therapy, including azithromycin, imipenem/cilastatin, levofloxacin, minocycline, linezolid, and sitafloxacin, the patient ultimately died of the infection. The patient tested negative for HIV and anti-IFN-γ autoantibodies. CONCLUSIONS: Since myasthenia gravis symptoms interfere with therapy, patients with GS and their physicians should carefully consider the antibacterial treatment options against disseminated NTM.


Assuntos
Pneumopatias/microbiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus , Doenças da Imunodeficiência Primária/complicações , Antibacterianos/uso terapêutico , Autoanticorpos/sangue , Quimioterapia Combinada , Evolução Fatal , Fluoroquinolonas/uso terapêutico , Soronegatividade para HIV , Humanos , Interferon gama/imunologia , Pneumopatias/complicações , Pneumopatias/imunologia , Masculino , Pessoa de Meia-Idade , Miastenia Gravis/complicações , Infecções por Mycobacterium não Tuberculosas/complicações , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/imunologia , Síndrome
13.
Cytokine Growth Factor Rev ; 53: 13-24, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32475759

RESUMO

COVID-19 mortality is strongly associated with the development of severe pneumonia and acute respiratory distress syndrome with the worst outcome resulting in cytokine release syndrome and multiorgan failure. It is becoming critically important to identify at the early stage of the infection those patients who are prone to develop the most adverse effects. Elevated systemic interleukin-6 levels in patients with COVID-19 are considered as a relevant parameter in predicting most severe course of disease and the need for intensive care. This review discusses the mechanisms by which IL-6 may possibly contribute to disease exacerbation and the potential of therapeutic approaches based on anti-IL-6 biologics.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Síndrome da Liberação de Citocina/tratamento farmacológico , Interleucina-6/antagonistas & inibidores , Pneumonia Viral/tratamento farmacológico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Síndrome da Liberação de Citocina/patologia , Síndrome da Liberação de Citocina/virologia , Humanos , Interleucina-6/sangue , Interleucina-6/imunologia , Pneumopatias/imunologia , Pneumopatias/patologia , Pneumopatias/virologia , Pandemias , Pneumonia Viral/mortalidade , Pneumonia Viral/patologia
14.
Int J Mol Sci ; 21(9)2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32354030

RESUMO

BACKGROUND: On the 31 December 2019, the World Health Organization (WHO) was informed of a cluster of cases of pneumonia of unknown origin detected in Wuhan City, Hubei Province, China. The infection spread first in China and then in the rest of the world, and on the 11th of March, the WHO declared that COVID-19 was a pandemic. Taking into consideration the mortality rate of COVID-19, about 5-7%, and the percentage of positive patients admitted to intensive care units being 9-11%, it should be mandatory to consider and take all necessary measures to contain the COVID-19 infection. Moreover, given the recent evidence in different hospitals suggesting IL-6 and TNF-α inhibitor drugs as a possible therapy for COVID-19, we aimed to highlight that a dietary intervention could be useful to prevent the infection and/or to ameliorate the outcomes during therapy. Considering that the COVID-19 infection can generate a mild or highly acute respiratory syndrome with a consequent release of pro-inflammatory cytokines, including IL-6 and TNF-α, a dietary regimen modification in order to improve the levels of adiponectin could be very useful both to prevent the infection and to take care of patients, improving their outcomes.


Assuntos
Antioxidantes/administração & dosagem , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Dieta , Suplementos Nutricionais , Pneumonia Viral/imunologia , Pneumonia Viral/terapia , Adiponectina/metabolismo , Ácido Ascórbico/administração & dosagem , Infecções por Coronavirus/metabolismo , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/metabolismo , Flavonoides/administração & dosagem , Humanos , Interleucina-6/imunologia , Interleucina-6/metabolismo , Pneumopatias/imunologia , Pneumopatias/metabolismo , Pneumopatias/terapia , Pandemias , Pneumonia Viral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
15.
Clin Chim Acta ; 508: 110-114, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32405080

RESUMO

BACKGROUND: We observe changes of the main lymphocyte subsets (CD16+CD56、CD19、CD3、CD4、and CD8) in COVID-19-infected patients and explore whether the changes are associated with disease severity. METHODS: One-hundred and fifty-four cases of COVID-19-infected patients were selected and divided into 3 groups (moderate group, severe group and critical group). The flow cytometry assay was performed to examine the numbers of lymphocyte subsets. RESULTS: CD3+, CD4+ and CD8 + T lymphocyte subsets were decreased in COVID-19-infected patients. Compared with the moderate group and the sever group, CD3+, CD4+ and CD8+ T cells in the critical group decreased greatly (P < 0.001, P = 0.005 or P = 0.001). CONCLUSIONS: Reduced CD3+, CD4+, CD8+ T lymphocyte counts may reflect the severity of the COVID-19. Monitoring T cell changes has important implications for the diagnosis and treatment of severe patients who may become critically ill.


Assuntos
Betacoronavirus/patogenicidade , Doenças Cardiovasculares/diagnóstico , Infecções por Coronavirus/diagnóstico , Diabetes Mellitus/diagnóstico , Pneumopatias/diagnóstico , Pneumonia Viral/diagnóstico , Subpopulações de Linfócitos T/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Complexo CD3/genética , Complexo CD3/imunologia , Antígenos CD4/genética , Antígenos CD4/imunologia , Antígenos CD8/genética , Antígenos CD8/imunologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/fisiopatologia , Diabetes Mellitus/imunologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/fisiopatologia , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Pneumopatias/imunologia , Pneumopatias/mortalidade , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pandemias , Seleção de Pacientes , Pneumonia Viral/imunologia , Pneumonia Viral/mortalidade , Pneumonia Viral/fisiopatologia , Prognóstico , Índice de Gravidade de Doença , Análise de Sobrevida , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia
16.
Immunology ; 160(2): 171-182, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32196653

RESUMO

The airway epithelium represents a physical barrier to the external environment acting as the first line of defence against potentially harmful environmental stimuli including microbes and allergens. However, lung epithelial cells are increasingly recognized as active effectors of microbial defence, contributing to both innate and adaptive immune function in the lower respiratory tract. These cells express an ample repertoire of pattern recognition receptors with specificity for conserved microbial and host motifs. Modern molecular techniques have uncovered the complexity of the lower respiratory tract microbiome. The interaction between the microbiota and the airway epithelium is key to understanding how stable immune homeostasis is maintained. Loss of epithelial integrity following exposure to infection can result in the onset of inflammation in susceptible individuals and may culminate in lung disease. Here we discuss the current knowledge regarding the molecular and cellular mechanisms by which the pulmonary epithelium interacts with the lung microbiome in shaping immunity in the lung. Specifically, we focus on the interactions between the lung microbiome and the cells of the conducting airways in modulating immune cell regulation, and how defects in barrier structure and function may culminate in lung disease. Understanding these interactions is fundamental in the search for more effective therapies for respiratory diseases.


Assuntos
Células Epiteliais/imunologia , Pneumopatias/imunologia , Pulmão/imunologia , Microbiota/imunologia , Mucosa Respiratória/imunologia , Imunidade Adaptativa , Remodelação das Vias Aéreas/imunologia , Homeostase/imunologia , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Imunidade nas Mucosas , Pulmão/citologia , Pulmão/microbiologia , Pneumopatias/microbiologia , Mucosa Respiratória/microbiologia
17.
Am J Respir Cell Mol Biol ; 63(2): 152-159, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32207982

RESUMO

Childhood pulmonary diseases not only cause childhood morbidity and mortality but also can cause long-term pulmonary impairment. The clinical management of many childhood pulmonary diseases is hampered by a limited understanding of the underlying pathophysiological mechanisms. Flow cytometry, which can be used to phenotype individual cell populations or isolate cells for downstream analysis, represents a crucial technology that can help to elucidate the pathophysiology of these conditions. Here, we describe a flow cytometry-based method for purification and characterization of cell populations in BAL from children. This includes assessment of the effect of cryopreservation on cell phenotype and frequency, a knowledge gap recently identified by an American Thoracic Society report on flow cytometry in lung samples. To our knowledge, this is the first study to simultaneously quantify alveolar macrophages, T cells (CD4 and CD8), B cells, natural killer cells, dendritic cells, granulocytes, and monocytes (CD16+/CD16-) in the BAL of children. The protocols described can be used to advance investigation of the pathophysiology of childhood pulmonary diseases.


Assuntos
Líquido da Lavagem Broncoalveolar/imunologia , Lavagem Broncoalveolar/métodos , Pré-Escolar , Feminino , Citometria de Fluxo/métodos , Granulócitos/imunologia , Humanos , Lactente , Contagem de Leucócitos/métodos , Pulmão/imunologia , Pneumopatias/imunologia , Macrófagos Alveolares/imunologia , Masculino , Monócitos/imunologia , Análise de Célula Única/métodos , Linfócitos T/imunologia
18.
BMJ Case Rep ; 13(3)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32169990

RESUMO

A 70-year-old man presented with acute respiratory failure, alveolar infiltrates and haemoptysis requiring supplemental oxygen. Flexible bronchoscopy with bronchoalveolar lavage identifies diffuse alveolar haemorrhage. Clinical and serological evaluations do not identify a precise aetiology and histopathology establishes the diagnosis of isolated pauci-immune pulmonary capillaritis. The patient received induction therapy with high dose methylprednisolone at 1000 mg/day for 5 days and weekly rituximab at 375 mg/m2 scheduled over 4 weeks. Although the patient demonstrated clinical improvement after the first week, he experienced a rapid relapse requiring mechanical ventilation. His induction rituximab regimen was continued and plasma exchange was initiated. Despite these therapies, the patient's condition deteriorated and passed away. Our case adds insight to the management of this rare entity and describes the use of plasma exchange as salvage therapy.


Assuntos
Capilares/patologia , Pneumopatias/imunologia , Pulmão/irrigação sanguínea , Insuficiência Respiratória/etiologia , Doença Aguda , Idoso , Lavagem Broncoalveolar , Broncoscopia/métodos , Quimioterapia Combinada , Evolução Fatal , Glucocorticoides/administração & dosagem , Glucocorticoides/uso terapêutico , Hemoptise/etiologia , Hemorragia/etiologia , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/uso terapêutico , Imunossupressão/efeitos adversos , Pulmão/patologia , Pneumopatias/tratamento farmacológico , Pneumopatias/patologia , Masculino , Metilprednisolona/administração & dosagem , Metilprednisolona/uso terapêutico , Troca Plasmática/métodos , Recidiva , Rituximab/administração & dosagem , Rituximab/uso terapêutico
19.
Int J Mol Sci ; 21(3)2020 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-32046322

RESUMO

In autoantibody-mediated autoimmune diseases, pathogenic autoantibodies generated by a failure of central or peripheral tolerance, have different effects mediated by a variety of mechanisms. Interestingly, even non-autoimmune chronic diseases have a set of disease-specific natural autoantibodies that are maintained for a long time. Because most of these natural autoantibodies target intracellular proteins or long non-coding RNAs, they are speculated to be non-pathological and have some important as yet unrecognized physiological functions such as debris clearance. Recently, we revealed a set of disease-specific natural autoantibodies of chronic pulmonary diseases with unknown etiology by protein arrays that enable detection of specific autoantibodies against >8000 targets. Surprisingly, some of the targeted antigens of disease-specific autoantibodies were subsequently reported by other laboratories as strongly associated with the disease, suggesting that these antigens reflect the pathology of each disease. Furthermore, some of these autoantibodies that target extracellular antigens might modify the original course of each disease. Here, we review the disease-specific natural autoantibodies of chronic pulmonary diseases, including chronic fibrosing idiopathic interstitial pneumonias, sarcoidosis, and autoimmune pulmonary alveolar proteinosis, and discuss their utility and effects.


Assuntos
Autoanticorpos , Pneumopatias/imunologia , Doenças Autoimunes/imunologia , Doença Crônica , Humanos , Fibrose Pulmonar Idiopática/imunologia , Proteinose Alveolar Pulmonar/imunologia , Sarcoidose/imunologia
20.
Int J Mol Sci ; 21(3)2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-32013006

RESUMO

Neutrophils have a prominent role in all human immune responses against any type of pathogen or stimulus. The lungs are a major neutrophil reservoir and neutrophilic inflammation is a primary response to both infectious and non-infectious challenges. While neutrophils are well known for their essential role in clearance of bacteria, they are also equipped with specific mechanisms to counter viruses and fungi. When these defense mechanisms become aberrantly activated in the absence of infection, this commonly results in debilitating chronic lung inflammation. Clearance of bacteria by phagocytosis is the hallmark role of neutrophils and has been studied extensively. New studies on neutrophil biology have revealed that this leukocyte subset is highly adaptable and fulfills diverse roles. Of special interest is how these adaptations can impact the outcome of an immune response in the lungs due to their potent capacity for clearing infection and causing damage to host tissue. The adaptability of neutrophils and their propensity to influence the outcome of immune responses implicates them as a much-needed target of future immunomodulatory therapies. This review highlights the recent advances elucidating the mechanisms of neutrophilic inflammation, with a focus on the lung environment due to the immense and growing public health burden of chronic lung diseases such as cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD), and acute lung inflammatory diseases such as transfusion-related acute lung injury (TRALI).


Assuntos
Pneumopatias/imunologia , Pulmão/imunologia , Neutrófilos/metabolismo , Fibrose Cística/imunologia , Homeostase , Humanos , Doença Pulmonar Obstrutiva Crônica/imunologia , Lesão Pulmonar Aguda Relacionada à Transfusão/imunologia
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